Abstract

In our efforts to meet the vitamin C requirements of dialysis patients we confront a medical dilemma - do we allow the patient to become depleted of vitamin C, with the accompanying hematological and other consequences (Scylla), or do we provide for adequate tissue levels of vitamin C, which has been thought to carry the risk of oxalosis (Charybdis). Many practitioners are certain that either one outcome (deficiency) or the other (oxalic acid toxicity) is inevitable, and much like Odysseus, no safe course is to be found. The recent accumulating evidence that vitamin C improves the management of anemia in dialysis patients compels us to find a safe passage through this dilemma. The serious vitamin C deficiency seen in many patients may also contribute to poor oral health and chronic fatigue. The evidence for oxalosis from vitamin C supplements stems from hemodialysis as practiced 20 years ago. Investigators using this therapy are not observing systemic oxalosis, and the most current data support the conclusion that vitamin C therapy is safe for dialysis patients. The question will be resolved by controlled trials that address both vitamin C effectiveness and safety.

In the Odyssey, the task set to Odysseus is to sail between the sea monster at Scylla and the whirlpool at Cha-rybdis. In the myth, a course away from one is virtually certain to lead to the other, although the myth opens the possibility that extraordinary seamanship might lead to safe passage. Are we faced with the same delicate balance in providing appropriate levels of vitamin C for dialysis patients?

Limited dietary intake of vitamin C has long been a major issue in dialysis therapy [1], Most dietary vitamin C is provided by foods such as orange juice, strawberries, and broccoli, which are rich in potassium. Since hyper-kalemia is a major risk factor for dialysis morbidity and mortality [2], the renal dietitian often instructs the patient to limit intake of potassium-rich foods [3]. Many of the best sources of vitamin C are excluded by these guidelines, and low dietary vitamin C intake can readily occur. The problem is aggravated by vitamin C losses during dialysis, which may remove several hundred milligrams of vitamin C in a single dialysis treatment [4, 5]. Normal plasma vitamin C levels in the nondialysis population are 30-60 ^M [6], By contrast, plasma vitamin C in dialysis patients is frequently <10 ^M [7], and may be as low as 2 ^M [Handelman, in preparation]. Vitamin C deficiency may be seen as Scylla, the sea monster that would doom the ship.

The appropriate response to restricted vitamin C intake from diet is to provide dietary vitamin C supplements. But here we are faced with the specter of Charyb-dis, the whirlpool. The metabolism of vitamin C includes the formation of oxalic acid, which has limited solubility in human tissues. When the plasma concentration of oxalate exceeds 40 ^M, there is at least the possibility of oxalate crystals forming in a variety of tissues, including retina, skin, joints, and cardiac muscle. This syndrome, called primary oxalosis, is often found in children with a metabolic defect that forms excessive oxalate in the liver. Primary oxalosis often leads to early kidney failure and death, and is only treatable by liver transplantation. Prior to the advent of reliable high-flux dialysis therapy, some cases of oxalosis were observed in patients with end-stage renal disease [ 8, 9]. Following implementation of 3x/ week dialysis therapy, with weekly standardized Kt/V >2, oxalate deposits could not be detected in a thorough biochemical analysis of biopsy and autopsy material from hemodialysis patients [10], and no case reports of oxalate deposition have been reported in recent years in dialysis patients as a result of vitamin C supplement use. However, the usual guidance provided in nephrology textbooks and manuals on renal nutrition is to 'limit dietary vitamin C supplements to 60 mg/day, to avoid oxalosis' [11]. For many patients, this dosage has not achieved the normal range of plasma vitamin C, and deficiency is widespread. For many in nephrology, oxalosis (Charyb-dis) seems the greater peril, and vitamin C deficiency (Scylla) is accepted as unavoidable.